Delayed and Precocious Puberty

  • Laurence J. Abernethy
  • Joanne C. Blair
  • Julie B. Smith
  • Mohammed A. Didi
Part of the Medical Radiology book series (MEDRAD)


Delayed and precocious puberty are distressing conditions that can have serious long-term effects, and may also be the presenting manifestation of serious underlying medical conditions affecting the hypothalamic-pituitary-gonadal axis. An understanding of the various disorders of sexual development is essential for rational radiological investigation and the interpretation of its findings. True (central) precocious puberty and precocious pseudopuberty must be distinguished from the variants of precocious sexual development that may have similar early clinical features (isolated premature menarche, isolated premature thelarche and thelarche variant, and isolated premature adrenarche). Before initiating radiological investigations, full clinical assessment is essential. Radiological investigations are important in both delayed and precocious puberty to provide additional indicators of the stage of puberty. The most important radiological indicators of stage of puberty are radiographic estimation of bone age, and ultrasound of the pelvis. Ultrasound assessment of the stage of development of the uterus and ovaries is a valuable tool in the diagnosis of precocious puberty in girls and in differentiating between true precocious puberty and other types of early puberty. Serial ultrasound is also useful to assess the response to treatment. Delayed and precocious puberty may be caused by intracranial pathology which disrupts the hypothalamic-pituitary axis. True precocious puberty in girls is idiopathic or familial in over 80% of cases, but cranial MRI is necessary to exclude CNS abnormalities. Hypothalamic hamartoma is the most common intracranial tumour identified in true precocious puberty. CNS lesions that may result in either delayed or precocious puberty include neurofibromatosis type 1 (usually in association with an optic pathway glioma), craniopharyngioma, and suprasellar lesions such as arachnoid cysts and epidermoid cysts. In pseudo-precocious puberty, pelvic ultrasound should be undertaken to assess the stage of development of the uterus and ovaries; the ovaries should also be carefully examined for evidence of an autonomously functioning ovarian cyst or tumour that secretes oestrogen (granulosa-theca cell tumours are the most common). A comprehensive ultrasound examination of the whole of the abdomen should also be undertaken, with particular attention to the adrenals for evidence of an adrenal tumour or diffuse bilateral hypertrophy.


Congenital Adrenal Hyperplasia Turner Syndrome Precocious Puberty Gonadal Dysgenesis Central Precocious Puberty 



Gonadotropin-Releasing Hormone


Thyroid-stimulating hormone


McCune-Albright syndrome


Multifollicular ovary


Traumatic brain-injury


Diabetes insipidus


Adrenocorticotropic Hormone


Growth hormone


Septo-optic dysplasia


Cyclic adenosine monophosphate


Serine/threonine kinase 11


Juvenile granulosa cell tumour


The International Federation of Gynecology and Obstetrics


Van Wyk-Grumbach syndrome


Guanine-nucleotide-binding protein α-subunit


Peutz-Jeghers syndrome


Sertoli-Leydig cell tumour


Polycystic ovary morphology




Basic fibroblast growth factor receptor 1




Prokineticin-2 receptor


Chromodomainhelicase-DNA-binding protein 7


Fibroblast Growth Factor 8


Colobomata, Heart defect, choanal Atresia, Retarded growth and development, Genital hypoplasia and Ear abnormalities and/or deafness


Langerhans cell histiocytosis




Central nervous system


Congenital Adrenal Hyperplasia


Adrenocortical tumours


Optic pathway glioma


Dehydroepiandrosterone sulphate

17 OHP



Magnetic Resonance


Neurofibromatosis type 1


Body mass-index


Computed Tomography


Magnetic Resonance Imaging


Cerebrospinal fluid


Luteinising hormone


Follicle stimulating hormone


POU class 1 homeobox 1


PROP paired-like homeobox 1


HESX homeobox 1


LIM homeobox 3 LHX3


LIM homeobox 4 LHX4


SRY (sex determining region Y)-box 2 sox-2


SRY (sex determining region Y)-box 3


T-box 19


  1. Abernethy LJ (1998) Imaging of the pituitary in children with growth disorders. Eur J Radiol 26:102–108Google Scholar
  2. Amato MC, Elias LL, Elias J et al (2006) Endocrine disorders in pediatric—onset Langerhans cell histiocytosis. Horm Metab Res 38:746–751PubMedCrossRefGoogle Scholar
  3. Anasti JN, Flack MR, Froehlich J et al (1995) A potential novelmechanism for precocious puberty in juvenile hypothyroidism. J Clin Endocrinol Metab 80:276–279PubMedCrossRefGoogle Scholar
  4. Argyropolou M, Perignon F, Brunelle F et al (1991) Height of normal pituitary gland as a function of age evaluated by MRI in children. Pediatr Radiol 21:247–249CrossRefGoogle Scholar
  5. Arslanian SA, Rothfus WE, Foley TP (1984) Hormonal, metabolic, and neuroradiologic abnormalities associated with septo-optic dysplasia. Acta Endocrinol 107:282–288PubMedGoogle Scholar
  6. Barral V, Brunelle F, Brauner R et al (1988) MRI of hypothalamic hamartomas in children. Pediatr Radiol 18:449–452PubMedCrossRefGoogle Scholar
  7. Battaglia C, Regnani G, Mancini F et al (2002) Pelvic sonography and uterine artery color doppler analysis in the diagnosis of female precocious puberty. Ultrasound Obstet Gynecol 19:386–391PubMedCrossRefGoogle Scholar
  8. Baumann DA, Landolt MA, Wetterwald R et al (2001) Psychological evaluation of young women after medical treatment for central precocious puberty. Horm Res 56:45–50PubMedCrossRefGoogle Scholar
  9. Bernstrand C, Sandstedt B, Ahström L et al (2005) Long-term follow-up of Langerhans cell histiocytosis: 39 years’ experience at a single centre. Acta Paediatr 94:1073–1084PubMedCrossRefGoogle Scholar
  10. Bondy CA (2007) Turner syndrome study group. Care of girls and women with Turner syndrome: a guideline of the Turner syndrome study group. J Clin Endocrinol Metab 92:10–25PubMedCrossRefGoogle Scholar
  11. Browne LP, Boswell HB, Crotty EJ et al (2008) Van Wyk and Grumbach syndrome revisited: imaging and clinical findings in pre- and postpubertal girls. Pediatr Radiol 38:538–542PubMedCrossRefGoogle Scholar
  12. Buzzi F, Pilotta A, Dordoni D et al (1998) Pelvic ultrasonography in normal girls and in girls with pubertal precocity. Acta Paediatr 87:1138–1145CrossRefGoogle Scholar
  13. Carel JC, Eugster EA, Rogol A et al ESPE-LWPES GnRH Analogs Consensus Conference Group (2009) Consensus statement on the use of gonadotropin-releasing hormone analogs in children. Pediatrics 123:e752–e762PubMedCrossRefGoogle Scholar
  14. Chateil J, Sousotte C, Pedespan J et al (2001) MRI and clinical differences between optic pathway tumours in children with and without neurofibromatosis. Br J Radiol 74:24–31PubMedGoogle Scholar
  15. Cronje′ HS, Niemand I, Bam RH et al (1998) Granulosa and theca cell tumors in children: a report of 17 cases and literature review. Obstet Gynecol Surv 53:240–247PubMedCrossRefGoogle Scholar
  16. de Vries L, Lazar L, Phillip M (2003a) Craniopharyngioma: presentation and endocrine sequelae in 36 children. J Pediatr Endocrinol Metab 16:703–710PubMedCrossRefGoogle Scholar
  17. de Vries L, Weintrob N, Phillip M (2003b) Craniopharyngioma presenting as precocious puberty and accelerated growth. Clin Pediatr 42:181–184CrossRefGoogle Scholar
  18. de Vries L, Horev G, Schwartz M et al (2006) Ultrasonographic and clinical parameters for early differentiation between precocious puberty and premature thelarche. Eur J Endocrinol 154:891–898PubMedCrossRefGoogle Scholar
  19. DeVile CJ, Grant DB, Hayward RD et al (1996) Growth and endocrine sequelae of craniopharyngioma. Arch Dis Child 75:108–114PubMedCrossRefGoogle Scholar
  20. Einaudi S, Matarazzo P, Peretta P et al (2006) Hypothalamo-hypophysial dysfunction after traumatic brain injury in children and adolescents: a preliminary retrospective and prospective study. J Pediatr Endocrinol Metab 19:691–703PubMedCrossRefGoogle Scholar
  21. Fahmy JL, Kaminsky CK, Kaufman F et al (2000) The radiological approach to precocious puberty. Br J Radiol 73:560–567PubMedGoogle Scholar
  22. Fujisawa I, Kikuchi K, Nishimura K et al (1987) Transection of the pituitary stalk: development of an ectopic posterior lobe assessed with MR imaging. Radiology 165:487–489PubMedGoogle Scholar
  23. Garel C, Leger J (2007) Contribution of magnetic resonance imaging in non-tumoral hypopituitarism in children. Horm Res 67:194–202PubMedCrossRefGoogle Scholar
  24. Greulich WW, Pyle SI (1959) Radiographic atlas of skeletal development of the hand and wrist, 2nd edn. Stanford University Press, Stanford, CaliforniaGoogle Scholar
  25. Griffin IJ, Donaldson TJ, Duncan KA et al (1995) Pelvic ultrasound measurements in normal girls. Acta Paediatr 84:536–543PubMedCrossRefGoogle Scholar
  26. Grois N, Prayer D, Prosch H et al (2004) Course and clinical impact of magnetic resonance imaging findings in diabetes insipidus associated with Langerhans cell histiocytosis. Pediatr Blood Cancer 43:59–65PubMedCrossRefGoogle Scholar
  27. Haber HP, Mayer EI (1994) Ultrasound evaluation of uterine and ovarian size form birth to puberty. Pediatr Radiol 24:11–13PubMedCrossRefGoogle Scholar
  28. Haber HP, Ranke MB (1999) Pelvic ultrasonography in Turner syndrome: standards for uterine and ovarian volume. J Ultrasound Med 18:271–276PubMedGoogle Scholar
  29. Harley VR, Clarkson MJ, Argentaro A (2003) The molecular action and regulation of the testis-determining factors, SRY (sex-determining region on the Y chromosome) and SOX9 [SRY-related high-mobility group (HMG) box 9]. Endocr Rev 24:466–487Google Scholar
  30. Heger S, Partsch CJ, Sippell WG (1999) Long-term outcome after depot gonadotropin-releasing hormone agonist treatment of central precocious puberty: final height, body proportions, body composition, bone mineral density, and reproductive function. J Clin Endocrinol Metab 84:4583–4590PubMedCrossRefGoogle Scholar
  31. Herter LD, Golendziner E, Flores JA et al (2002) Ovarian and uterine findings in pelvic sonography. Comparison between prepubertal girls, girls with isolated thelarche, and girls with central precocious puberty. J Ultrasound Med 21:1237–1246PubMedGoogle Scholar
  32. Ho VB, Bakalov VK, Cooley M (2004) Major vascular anomalies in Turner syndrome. Circulation 110:1694–1700PubMedCrossRefGoogle Scholar
  33. Izenberg N, Rosenblum M, Parks JS (1984) The endocrine spectrum of septo-optic dysplasia. Clin Pediatr 23:632–636CrossRefGoogle Scholar
  34. Kaatsch P, Rickert CH, Kühl J et al (2001) Population-based epidemiologic data on brain tumors in German children. Cancer 92:3155–3164PubMedCrossRefGoogle Scholar
  35. Kalfa N, Méduri G, Philibert P et al (2010) Unusual virilization in girls with juvenile granulosa cell tumors of the ovary is related to intratumoral aromatase deficiency. Horm Res Paediatr 74:83–91PubMedCrossRefGoogle Scholar
  36. Kelberman D, Dattani MT (2007) Hypothalamic and pituitary development: novel insights into the aetiology. Eur J Endocrinol 157:S3–S14PubMedCrossRefGoogle Scholar
  37. Kikuchi K, Fujisawa I, Momoi T et al (1988) Hypothalamic-pituitary function in growth hormone-deficient patients with pituitary stalk transection. J Clin Endocrinol Metab 67:817–823PubMedCrossRefGoogle Scholar
  38. Klein KO, Larmore KA, de Lancey E et al (1998) Effect of obesity on estradiol level, and its relationship to leptin, bone maturation, and bone mineral density in children. J Clin Endocrinol Metab 83:3469–3475PubMedCrossRefGoogle Scholar
  39. Klein KO, Barnes KM, Jones JV et al (2001) Increased final height in precocious puberty after long term treatment with LHRH agonists: the National Institutes of Health experience. J Clin Endocrinol Metab 86:4711–4716PubMedCrossRefGoogle Scholar
  40. Lazar L, Kauli R, Pertzelan A et al (2002) Gonadotropin-suppressive therapy in girls with early and fast puberty affects the pace of puberty but not total pubertal growth or final height. J Clin Endocrinol Metab 87:2090–2094PubMedCrossRefGoogle Scholar
  41. Lumbroso S, Paris F, Sultan C (2004) Activating Gsalpha Mutations: Analysis of 113 Patients with Signs of McCune-Albright Syndrome - A European Collaborative Study. J Clin Endocrinol Metab 89:2107–2113PubMedCrossRefGoogle Scholar
  42. May JA, Krieger MD, Bowen I et al (2006) Craniopharyngioma in childhood. Adv Pediatr 53:183–209PubMedCrossRefGoogle Scholar
  43. Mazzanti L, Cacciari E, Bergamaschi R et al (1997) Pelvic ultrasonography in patients with Turner syndrome: Age-related findings in different karyotypes. J Pediatr 131:135–140PubMedCrossRefGoogle Scholar
  44. Mazzanti L, Cicognani A, Baldazzi L et al (2005) Gonadoblastoma in Turner syndrome and Y-chromosome-derived material. Am J Med Genet A 135:150–154PubMedGoogle Scholar
  45. McNay DE, Turton JP, Kelberman D et al (2007) HESX1 mutations are an uncommon cause of septooptic dysplasia and hypopituitarism. J Clin Endocrinol Metab 92:691–697PubMedCrossRefGoogle Scholar
  46. Nanduri VR, Bareille P, Pritchard J et al (2000) Growth and endocrine disorders in multisystem Langerhans’ cell histiocytosis. Clin Endocrinol 53:509–515CrossRefGoogle Scholar
  47. New MI, Lorenzen F, Lerner AJ et al (1983) Genotyping steroid 21-hydroxylase deficiency: hormonal reference data. J Clin Endocrinol Metab 57:320–326PubMedCrossRefGoogle Scholar
  48. Ng SM, Kumar Y, Cody D, Smith CS, Didi M (2003) Cranial MRI scans are indicated in all girls with central precocious puberty. Arch Dis Child 88:414–418PubMedCrossRefGoogle Scholar
  49. Ng SM, Kumar Y, Cody D, Smith CS, Didi M (2005) The gonadotrophins response to GnRH test is not a predictor of neurological lesion in girls with central precocious puberty. J Pediatr Endocrinol Metab 18:849–852PubMedCrossRefGoogle Scholar
  50. Niederland T, Makovi H, Gál V et al (2007) Abnormalities of pituitary function after traumatic brain injury in children. J Neurotrauma 24:119–127PubMedCrossRefGoogle Scholar
  51. Outwater EK, Wagner BJ, Mannion C et al (1998) Sex cord-stromal and steroid cell tumors of the ovary. Radiographics 18:1523–1546PubMedGoogle Scholar
  52. Pallais JC, Au M, Pitteloud N et al (2010) Kallmann syndrome. In: Pagon RA, Bird TC, Dolan CR, Stephens K (eds). GeneReviews [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2007 May 23 [updated 2010 Apr 8] Accessed Aug 2010Google Scholar
  53. Patel L, McNally RJ, Harrison E et al (2006) Geographical distribution of optic nerve hypoplasia and septo-optic dysplasia in Northwest England. J Pediatr 148:85–88PubMedCrossRefGoogle Scholar
  54. Paterson WF, McNeill E, Young D, Donaldson MD (2004) Auxological outcome and time to menarche following long-acting goserelin therapy in girls with central precocious or early puberty. Clin Endocrinol (Oxf) 61:626–634CrossRefGoogle Scholar
  55. Pescovitz OH, Hench KD, Barnes KM et al (1988) Premature thelarche and central precocious puberty: the relationship between clinical presentation and the gonadotropin response to luteinizing hormone-releasing hormone. J Clin Endocrinol Metab 67:474–479PubMedCrossRefGoogle Scholar
  56. Pinto SM, Garden AS (2006) Prepubertal menarche: a defined clinical entity. Am J Obstet Gynecol 195:327–329PubMedCrossRefGoogle Scholar
  57. Plantaz D, Flamant F, Vassal G et al (1992) Granulosa cell tumors of the ovary in children and adolescents. Multicenter retrospective study in 40 patients aged 7 months–22 years]. Arch Fr Pediatr 49:793PubMedGoogle Scholar
  58. Poomthavorn P, Maixner W, Zacharin M (2008) Pituitary function in paediatric survivors of severe traumatic brain injury. Arch Dis Child 93:133–137PubMedCrossRefGoogle Scholar
  59. Roche AF, Chumlea WC, Thissen D (1988) Assessing the skeletal maturity of the hand-wrist: FELS method. Charles C Thomas, Springfield, IllinoisGoogle Scholar
  60. Rosenfield RL, Lipton RB, Drum ML (2009) Thelarche, Pubarche, and Menarche attainment in children with normal and elevated body mass index. Pediatrics 123:84–88PubMedCrossRefGoogle Scholar
  61. Sampaolo P, Calcaterra V, Klersy C et al (2003) Pelvic ultrasound evaluation in patients with Turner syndrome during treatment with growth hormone. Ultrasound Obstet Gynecol 22:172–177PubMedCrossRefGoogle Scholar
  62. Schneider JF, Floemer F (2009) Maturation of the olfactory bulbs: MR imaging findings. Am J Neuroradiol 30:1149–1152PubMedCrossRefGoogle Scholar
  63. Sklar CA (1994) Craniopharyngioma: endocrine abnormalities at presentation. Pediatr Neurosurg 21(Suppl 1):18–20PubMedCrossRefGoogle Scholar
  64. Stanhope R, Brook CC (1990) Thelarche variant: a new syndrome of precocious sexual maturation? Acta Endocrinol 123:481–486PubMedGoogle Scholar
  65. Street ME, Weber A, Camacho-Hübner C et al (1997) Girls with virilisation in childhood: a diagnostic protocol for investigation. J Clin Pathol 50:379–383PubMedCrossRefGoogle Scholar
  66. Suzuki M, Takashima T, Kadoya M et al (1989) MR imaging of olfactory bulbs and tracts. Am J Neuroradiol 10:955–957PubMedGoogle Scholar
  67. Sybert VP, McCauley E (2004) Turner’s syndrome. New Eng J Med 351:1227–1238PubMedCrossRefGoogle Scholar
  68. Tanner JM, Whitehouse RH, Cameron N et al (eds) (1983) Assessment of skeletal maturity and prediction of adult height (TW2 method), 2nd edn. Academic Press, LondonGoogle Scholar
  69. Truwit CL, Barkovich AJ, Grumbach MM et al (1993) MR imaging of Kallmann syndrome: a genetic disorder of neuronal migration affecting the olfactory and genital systems. Am J Neuroradiol 14:827–838PubMedGoogle Scholar
  70. Weinstein LS, Shenker A, Gejman PV et al (1991) Activating mutations of the stimulatory G protein in the McCune-Albright syndrome. N Engl J Med 325:1688–1695PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2011

Authors and Affiliations

  • Laurence J. Abernethy
    • 1
  • Joanne C. Blair
    • 2
  • Julie B. Smith
    • 1
  • Mohammed A. Didi
    • 2
  1. 1.Department of RadiologyAlder Hey Children’s NHS Foundation TrustLiverpoolUK
  2. 2.Department of EndocrinologyAlder Hey Children’s NHS Foundation TrustLiverpoolUK

Personalised recommendations